Effects of Quinolinic and Kynurenic Acids on Central Neurons

  • T. W. Stone
  • J. H. Connick
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 294)


Interest in the cellular basis of the actions of kynurenines in the central nervous system can be dated to 1981 when a range of cyclic analogs of the excitatory amino acids glutamate and aspartate were tested on the excitability of neurons in the cerebral cortex of anesthetised rats (Stone and Perkins, 1981; Stone, 1984). The earliest observations were of an excitatory action of quinolinic acid on cortical neurons, an action which clearly provided some explanation for the convulsant effects of quinolinic acid reported previously by Lapin and his colleagues (see Lapin, 1989). The excitation is summarized in histogram form in Fig. 1 which also reveals one of the major properties of quinolinic acid excitation also discovered in 1981. This is the sensitivity of the response to antagonism by compounds known to be active at the population of dicarboxylic amino acid receptors which show a preference for activation by N-methyl-D-aspartate (NMDA). Thus, in Fig. 1, the cell recorded in this case in the hippocampus in vivo was excited by applications of quinolinic acid, NMDA and quisqualic acid all applied by microiontophoresis from glass micropipettes on to a single neuron in the CA1 region of the hippocampal formation. The iontophoresis of 2-amino-5-phosphonopentanoic acid (2AP5) is then able to prevent excitation in response to both quinolinic acid and NMDA, the response to quisqualic acid being unchanged.


NMDA Receptor Kainic Acid Quinolinic Acid Kynurenic Acid Ibotenic Acid 
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  1. Burton, N.R., Smith, D.A.S., and Stone, T.W., 1987, The mouse neocortical slice preparation and the pharmacology of excitatory neocortical amino acids, Comp. Biochem. Physiol., 88: 47–55.Google Scholar
  2. Burton, N.R., Smith, D.A.S., and Stone, T.W., 1938, A quantitative pharmacological analysis of excitatory amino acid receptors in the mouse neocortex in vitro, Br. J. Pharmacol., 93: 693–702.Google Scholar
  3. Connick, J.H., Carlà, V., Moroni, F., and Stone, T.W., 1989, Increase in kynurenic acid in Huntington’s disease motor cortex, J. Neurochem., 52: 985–987.PubMedCrossRefGoogle Scholar
  4. Connick, J.H., Stone, T.W., Carlà, V., and Moroni, F., 1988, Increased kynurenic acid in Huntington’s disease, Lancet, 2: 1373.PubMedCrossRefGoogle Scholar
  5. Foster, A.C., Vezzani, A., French, E.D., and Schwarcz, R., 1984, Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid, Neurosci. Lett., 48: 273–278.PubMedCrossRefGoogle Scholar
  6. Ganong, A.H., and Cotman, C.W., 1986, Kynurenic acid and quinolinic acid act at NMDA receptors in the rat hippocampus, J. Pharmacol. Exp. Therap., 236: 293–299.Google Scholar
  7. Ganong, A.H., Lanthorn, T.H., and Cotman, C.W., 1983, Kynurenic acid inhibits synaptic and acidic amino acid induced responses in the rat hippocampus and spinal cord, Brain Res., 273: 170–174.PubMedCrossRefGoogle Scholar
  8. Harrison, N.L., and Simmonds, M.A., 1985, Quantitative studies on some antagonists of NMDA in slices of rat cerebral cortex, Br. J. Pharmacol., 84: 381–392.PubMedGoogle Scholar
  9. Johnson, J.W., and Ascher, P., 1987, Glycine potentiates the NMDA responses in cultured mouse brain neurons, Nature, 325: 529–531.PubMedCrossRefGoogle Scholar
  10. Lapin, I.P., 1989, Behavioral and convulsant effects of kynurenines, in: “Quinolinic Acid and the Kynurenines”, Stone, T.W., ed., CRC Press, Boca Raton, pp. 193–212.Google Scholar
  11. Perkins, M.N., and Stone, T.W., 1981, An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid, Brain Res., 247: 184–187.CrossRefGoogle Scholar
  12. Perkins, M.N., and Stone, T.W., 1983, Pharmacology and regional variations of quinolinic acid evoked excitations in the rat CNS, J. Pharmacol. Exp. Therap., 226: 551–556.Google Scholar
  13. Perkins, M.N., and Stone, T.W., 1985, Actions of kynurenic acid and quinolinic acid in the rat hippocampus in vivo. Exp. Neurol., 88: 570–579.PubMedCrossRefGoogle Scholar
  14. Pinelli, A., Govoni, S., Ossi, C., Battaini, F., Caimi, B.R., and Trivulzio, S., 1985, Kynurenine may directly interact with GABA receptors in brain, Pharmacology, 30: 255–258.PubMedCrossRefGoogle Scholar
  15. Shalaby, I., Chenard, B., and Prochniak, M., 1989, Glycine reverses 7-chlorokynurenate block of glutamate neurotoxicity in cell culture, Eur. J. Pharmacol., 160: 309.PubMedCrossRefGoogle Scholar
  16. Stone, T.W., 1984, Excitant activity of methyl derivatives of quinolinic acid on rat cortical neurons, Br. J. Pharmacol., 81: 175–181.PubMedGoogle Scholar
  17. Stone, T.W., 1985, “Microiontophoresis and Pressure Ejection”, Wiley, Chichester.Google Scholar
  18. Stone, T.W., 1988, Comparison of kynurenic acid and 2APV suppression of epileptiform activity in rat hippocampal slices, Neurosci. Lett., 84: 234–238.PubMedCrossRefGoogle Scholar
  19. Stone, T.W., and Burton, N.R., 1988, NMDA receptors and ligands in the vertebrate CNS, Progr. Neurobiol., 30: 333–368.CrossRefGoogle Scholar
  20. Stone, T.W., and Perkins, M.N., 1981, Quinolinic acid: a potent endogenous excitant at amino acid receptors in rat CNS, Eur. J. Pharmacol., 72: 411–412.PubMedCrossRefGoogle Scholar
  21. Stone, T.W., and Perkins, M.N., 1984, Actions of amino acids and kynurenic acid in the primate hippocampus, Neurosci. Lett., 52: 335–340.PubMedCrossRefGoogle Scholar
  22. Williams, T.L.M., Smith, D.A.S., Burton, N.R., and Stone, T.W., 1988, Amino acid pharmacology in neocortical slices: evidence for bimolecular actions from an extension of the Hill and Gaddum-Schild equations, Br. J. Pharmacol., 95: 805–810.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • T. W. Stone
    • 1
  • J. H. Connick
    • 1
  1. 1.Department of PharmacologyUniversity of GlasgowScotland

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